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Protective role of TNF-α, IL-10 and IL-2 in mice infected with the Oshima strain of Tick-borne encephalitis virus.

Tun MM, Aoki K, Senba M, Buerano CC, Shirai K, Suzuki R, Morita K, Hayasaka D - Sci Rep (2014)

Bottom Line: Tick-borne encephalitis virus (TBEV) causes acute central nervous system disease.However, viral loads and proinflammatory cytokine levels in the brain of TNF-α KO andIL-10 KO mice were not significantly different compared with those of WT mice.From these results, we suggest that TNF-α, IL-10 and IL-2 are key factors for disease remission from fatal encephalitis due to infection with Oshima strain of TBEV.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Institute of Tropical Medicine, Leading Graduate School Program, Nagasaki University, 852-8523, Nagasaki, Japan.

ABSTRACT
Tick-borne encephalitis virus (TBEV) causes acute central nervous system disease. Here, we investigated the roles of the TNF-α, IL-10 and other cytokines in appropriate KO mice following infection with Oshima and Sofjin strains of TBEV. Following infection with the Oshima strain, mortality rates were significantly increased in TNF-α KO and IL-10 KO mice compared with wild type (WT) mice. These results suggested that TNF-α and IL-10 play protective roles against fatal infection due to Oshima strain infection. However, viral loads and proinflammatory cytokine levels in the brain of TNF-α KO andIL-10 KO mice were not significantly different compared with those of WT mice. On the other hand, all WT, TNF-α KO and IL-10 KO mice died following infection with Sofjin strain. Interestingly, Sofjin-infected mice did not exhibit an up-regulated mRNA level of IL-2 in the spleen in all groups of mice, whereas Oshima-infected mice showed significantly increased level of IL-2 compared with mock-infected mice. From these results, we suggest that TNF-α, IL-10 and IL-2 are key factors for disease remission from fatal encephalitis due to infection with Oshima strain of TBEV.

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Related in: MedlinePlus

mRNA levels of IFN-γ, IL-2, IL-4, IL-6, IL-10 and TNF-α quantified by real time PCR in the brain of WT, IL-10 KO and TNF-α KO mice (n = 4 to 10) infected with 104 pfu of Oshima (a) and Sofjin (b) at 5 and 9 days pi.
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f3: mRNA levels of IFN-γ, IL-2, IL-4, IL-6, IL-10 and TNF-α quantified by real time PCR in the brain of WT, IL-10 KO and TNF-α KO mice (n = 4 to 10) infected with 104 pfu of Oshima (a) and Sofjin (b) at 5 and 9 days pi.

Mentions: The following levels were observed in the brain of specific group of Oshima-infected mice as compared with that of the mock-infected mice (Supplementary Figure 2a): (i) significantly higher levels of IFN-γ and of IL-2 at 9 days pi or at both 5 and 9 days pi in each of the three groups of mice, (ii) significantly higher level of IL-6 at 9 days pi in WT and IL-10 KO mice but not in TNF-α KO mice, (iii) significantly higher level of TNF-α in WT at both 5 and 9 days pi and in IL-10 KO mice at 9 days pi, and (iv) no significant difference in IL-4 level among the three groups nor in IL-10 level in WT and TNF-α KO groups at both 5 and 9 days pi. Of note, the levels of each cytokine observed were not significantly different between WT, IL-10 KO and TNF-α KO groups of mice after Oshima infection (Figure 3a). These observations suggest that inflammatory responses due to these cytokines in the brain could not be responsible to the increase of mortality observed in IL-10 KO and TNF-α KO mice.


Protective role of TNF-α, IL-10 and IL-2 in mice infected with the Oshima strain of Tick-borne encephalitis virus.

Tun MM, Aoki K, Senba M, Buerano CC, Shirai K, Suzuki R, Morita K, Hayasaka D - Sci Rep (2014)

mRNA levels of IFN-γ, IL-2, IL-4, IL-6, IL-10 and TNF-α quantified by real time PCR in the brain of WT, IL-10 KO and TNF-α KO mice (n = 4 to 10) infected with 104 pfu of Oshima (a) and Sofjin (b) at 5 and 9 days pi.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061546&req=5

f3: mRNA levels of IFN-γ, IL-2, IL-4, IL-6, IL-10 and TNF-α quantified by real time PCR in the brain of WT, IL-10 KO and TNF-α KO mice (n = 4 to 10) infected with 104 pfu of Oshima (a) and Sofjin (b) at 5 and 9 days pi.
Mentions: The following levels were observed in the brain of specific group of Oshima-infected mice as compared with that of the mock-infected mice (Supplementary Figure 2a): (i) significantly higher levels of IFN-γ and of IL-2 at 9 days pi or at both 5 and 9 days pi in each of the three groups of mice, (ii) significantly higher level of IL-6 at 9 days pi in WT and IL-10 KO mice but not in TNF-α KO mice, (iii) significantly higher level of TNF-α in WT at both 5 and 9 days pi and in IL-10 KO mice at 9 days pi, and (iv) no significant difference in IL-4 level among the three groups nor in IL-10 level in WT and TNF-α KO groups at both 5 and 9 days pi. Of note, the levels of each cytokine observed were not significantly different between WT, IL-10 KO and TNF-α KO groups of mice after Oshima infection (Figure 3a). These observations suggest that inflammatory responses due to these cytokines in the brain could not be responsible to the increase of mortality observed in IL-10 KO and TNF-α KO mice.

Bottom Line: Tick-borne encephalitis virus (TBEV) causes acute central nervous system disease.However, viral loads and proinflammatory cytokine levels in the brain of TNF-α KO andIL-10 KO mice were not significantly different compared with those of WT mice.From these results, we suggest that TNF-α, IL-10 and IL-2 are key factors for disease remission from fatal encephalitis due to infection with Oshima strain of TBEV.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Institute of Tropical Medicine, Leading Graduate School Program, Nagasaki University, 852-8523, Nagasaki, Japan.

ABSTRACT
Tick-borne encephalitis virus (TBEV) causes acute central nervous system disease. Here, we investigated the roles of the TNF-α, IL-10 and other cytokines in appropriate KO mice following infection with Oshima and Sofjin strains of TBEV. Following infection with the Oshima strain, mortality rates were significantly increased in TNF-α KO and IL-10 KO mice compared with wild type (WT) mice. These results suggested that TNF-α and IL-10 play protective roles against fatal infection due to Oshima strain infection. However, viral loads and proinflammatory cytokine levels in the brain of TNF-α KO andIL-10 KO mice were not significantly different compared with those of WT mice. On the other hand, all WT, TNF-α KO and IL-10 KO mice died following infection with Sofjin strain. Interestingly, Sofjin-infected mice did not exhibit an up-regulated mRNA level of IL-2 in the spleen in all groups of mice, whereas Oshima-infected mice showed significantly increased level of IL-2 compared with mock-infected mice. From these results, we suggest that TNF-α, IL-10 and IL-2 are key factors for disease remission from fatal encephalitis due to infection with Oshima strain of TBEV.

Show MeSH
Related in: MedlinePlus